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Biomedical subjects

J van Steveninck

Publications and source records attributed to J van Steveninck.

At least 19 recordsLinked to original sources
PubMed1994

Relationship between photodynamically induced damage to various cellular parameters and loss of clonogenicity in different cell types with hematoporphyrin derivative as sensitizer.

The possible causal relationship between various forms of photodynamically inflicted damage and reproductive cell death of cultivated cells was evaluated according to three criteria. The probability for the existence of such a relationship is high, when the particular form of cellular damage (i) exhibits a dose-effect curve, comparable to the dose-effect curve of loss of clonogenicity, (ii) is not readily repairable during further incubation of the treated cells and (iii) varies in a way comparable to the loss of clonogenicity under varying experimental conditions. According to these criteria it could be shown that many forms of photodynamically inflicted cellular damage are presumably not directly involved in loss of clonogenicity. Only for a few kinds of cellular damage studied in the present investigations was the probability for a causal relationship with reproductive cell death much higher. For L929 fibroblasts this is either an inhibition of the Na+/K(+)-ATPase activity, or a relatively slight DNA damage combined with a strong inhibition of DNA excision repair. For T24 human bladder carcinoma cells the kinds of cellular damage that may be causally related to reproductive cell death are again inhibition of Na+/K(+)-ATPase activity, inhibition of amino-acid (AIB and glycine) transport activity or impairment of mitochondrial function. Finally, for CHO cells, inhibition of leucine and phenylalanine transport and impairment of mitochondrial function may be crucial for loss of clonogenicity. These results indicate that the pathways leading to photodynamically induced reproductive cell death may be quite different for different cell types.

Animals↗
PubMed1994

The pro- and antioxidant properties of protoporphyrin IX.

The effect of protoporphyrin on lipid peroxidation in rat liver microsomes was investigated in the presence and absence of light. Protoporphyrin and light stimulated Fe(3+)-ADP/ascorbate-induced lipid peroxidation, whereas Fe(3+)-ADP/NADPH-mediated lipid peroxidation was inhibited. In the dark, on the other hand, protoporphyrin inhibited lipid peroxidation in both systems in a concentration-dependent manner. Protoporphyrin did not affect the reduction of the Fe(3+)-ADP complex by ascorbate, nor did it affect the activity of the NADPH-cytochrome P-450 reductase under these conditions. Uroporphyrin, a hydrophilic porphyrin and not localized in the membrane, did not inhibit lipid peroxidation in the dark in these systems, whereas bilirubin, a well-known radical scavenger and degradation product of protoporphyrin, inhibited lipid peroxidation in both systems. When peroxyl radicals were generated in solution by the azocompound 2,2'-azobis (2-amidino-propane)dihydrochloride lipid peroxidation was inhibited by both porphyrins and bilirubin. Reaction of bilirubin or protoporphyrin, in the presence of microsomes or human serum albumin, with these peroxyl radicals resulted in degradation of both compounds, which could be determined by a decrease in their absorbance at 460 or 407 nm, respectively. These results indicate that the inhibition of lipid peroxidation is most likely caused by scavenging of peroxyl radicals by protoporphyrin. Massive accumulation of protoporphyrin occurs in livers of erythropoietic protoporphyria patients. The fact that protoporphyrin was able to inhibit lipid peroxidation completely at micromolar concentrations also indicates that the deleterious effects of protoporphyrin, observed in these patients, are most likely not mediated by oxidation of lipids.

Adenosine Diphosphate↗
PubMed1992

Exocytosis in electropermeabilized neutrophils. Responsiveness to calcium and guanosine 5'-[gamma-thio]triphosphate.

Electropermeabilized neutrophils were used to study the exocytotic response in rabbit neutrophils. Enzyme release from electropermeabilized neutrophils could be induced by elevating the Ca2+ concentration. Ca(2+)-induced secretion was significantly enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[S]) in a concentration-dependent manner. The effect of GTP[S] could be blocked by guanosine 5'-[beta-thio]diphosphate (GDP[S]) and was not affected by pertussis toxin. GTP[S] did not induce enzyme release in the absence of Ca2+. Induction of an exocytotic response did not require addition of ATP. However, neutrophils permeabilized in the absence of ATP became refractory to stimulation due to a reduction in their affinity for Ca2+. Responsiveness to the effectors Ca2+ or Ca2+ + GTP[S] could be prolonged or restored by ATP. ATP was not the only agent that prolonged responsiveness; other nucleotides and inorganic phosphates were also effective. The protein kinase C inhibitors staurosporine and 1-O-hexadecyl-2-methyl-sn-glycerol did not inhibit exocytosis and had only a small effect on the prolongation and restoration of responsiveness by ATP. A hypothesis is presented suggesting that the loss of responsiveness is caused by dephosphorylation and that the restoration or prolongation of responsiveness is not mediated by protein kinase C. It is possible that an as yet unidentified Ca(2+)-binding protein is dephosphorylated, resulting in a decrease in Ca2+ affinity.

Adenosine Triphosphate↗
PubMed1991

Anomalous properties of water in macromolecular gels.

Low molecular weight solutes often exhibit elution characteristics on gel filtration columns which deviate from ideal behaviour. In many previous studies this anomalous behaviour was attributed to the existence of extremely narrow pores in the gel, inaccessible even to very small solute molecules, to explain Kd values lower than unity. Kd values of small solutes higher than unity were usually ascribed to adsorption of the solute to the gel matrix. In the present paper several observations are presented that contradict these suggestions. Experimental evidence indicates that with small solute molecules Kd values differing from unity can be fully explained by the anomalous properties of vicinal water layers at the gel matrix-water interface.

Chromatography, Gel↗
PubMed1991

Inhibition of neutrophil migration by guanine nucleotides.

Guanine nucleotides have, besides an activating effect on exocytosis and respiratory burst in permeabilized neutrophils, a modulating effect on some functions in intact neutrophils. We investigated the effect of guanine nucleotides on fMet-Leu-Phe-induced migration of rabbit neutrophils using the Boyden chamber technique. GTP gave a moderate inhibition of fMet-Leu-Phe-induced neutrophil migration. The GTP analogue GTP[S] had a stronger inhibitory effect than GTP. Other nucleotides, such as GDP, GMP, and guanosine were less effective inhibitors than GTP and GTP[S]. Maximal inhibition was achieved at nucleotide concentration of about 40 microM; higher concentration gave only little additional inhibition. The inhibitory effect persisted when the nucleotide was removed after pretreatment of the neutrophil with that nucleotide. Guanine nucleotide induced inhibition was not due to an interference with the fMet-Leu-Phe receptor as casein-induced migration was equally inhibited. We recently found that ATP inhibited neutrophil chemotaxis. The results obtained with guanine nucleotides resembles the inhibitory effects of ATP and its analogues. It is conceivable that guanine nucleotide-induced inhibition of neutrophil migration is mediated by an interaction of these nucleotides with purinergic receptors.

Animals↗
PubMed1989

Polyphosphate synthesis in yeast.

Polyphosphate synthesis was studied in phosphate-starved cells of Saccharomyces cerevisiae and Kluyveromyces marxianus. Incubation of these yeasts for a short time with phosphate and either glucose or ethanol resulted in the formation of polyphosphate with a short chain length. With increasing incubation times, polyphosphates with longer chain lengths were formed. Polyphosphates were synthesized faster during incubation with glucose than with ethanol. Antimycin did not affect the glucose-induced polyphosphate synthesis in either yeast. Using ethanol as an energy source, antimycin A treatment blocked both polyphosphate synthesis and accumulation of orthophosphate in the yeast S. cerevisiae. However, in K. marxianus, polyphosphate synthesis and orthophosphate accumulation proceeded normally in antimycin-treated cells, suggesting that endogenous reserves were used as energy source. This was confirmed in experiments, conducted in the absence of an exogenous energy source.

Adenosine Triphosphate↗
PubMed1988

The influence of ATP on sugar uptake mediated by the constitutive glucose carrier of Saccharomyces cerevisiae.

The glucose carrier of Saccharomyces cerevisiae transports the phosphorylatable sugars glucose, mannose, fructose and 2-deoxy-D-glucose (2-dGlc) and the non-phosphorylatable sugar 6-deoxy-D-glucose (6-dGlc). Reduction of the ATP concentration by, for example, incubating cells with antimycin A, results in a decrease in uptake of 2-dGlc and fructose. These uptake velocities can be increased again by raising the ATP level. These results establish a role of ATP in sugar transport. Transport of glucose and mannose is less affected by changes in the ATP concentration than 2-dGlc and fructose uptake, while the 6-dGlc transport is independent of the amount of ATP in the cells. Also, reduction of the kinase activity by incubation with xylose diminished transport of 2-dGlc and fructose, while the uptake of glucose and mannose remained unchanged. It is discussed that these results are due to transport-associated phosphorylation with ATP as substrate and the hexokinases and the glucokinase as phosphorylating enzymes.

Adenosine Triphosphate↗
PubMed1988

Inhibition of lipid peroxidation by disulfiram and diethyldithiocarbamate does not prevent hepatotoxin-induced cell death in isolated rat hepatocytes. A study with allyl alcohol, tert-butyl hydroperoxide, diethyl maleate, bromoisovalerylurea and carbon tetrachloride.

The relationship between lipid peroxidation and cell death, induced by a number of hepatotoxins, was studied in isolated rat hepatocytes. Disulfiram (DSF) and diethyldithiocarbamate (DDC) completely prevented lipid peroxidation, induced by allyl alcohol, tert-butyl hydroperoxide (t-BHP), diethyl maleate (DEM), bromoisovalerylurea (BIU) and carbon tetrachloride (CCl4). Lipid peroxidation was measured by the formation of both thiobarbituric acid positive material and conjugated dienes. However, DSF and DDC did not protect against cell death, induced by these hepatotoxins. In the presence of DSF or DDC, cell death occurred even earlier in time. We conclude that cell death can occur in the absence of lipid peroxidation. Therefore, lipid peroxidation is not a requisite for the induction of cell death.

1-Propanol↗
PubMed1987

Photodynamic effects of hematoporphyrin-derivative on enzyme activities of murine L929 fibroblasts.

Photodynamic treatment of murine L929 fibroblasts with hematoporphyrin-derivative resulted in the inactivation of cytosolic, mitochondrial and lysosomal enzymes and in a decrease in cellular adenosine triphosphate and reduced glutathione concentrations. Comparison of these results with those of previous studies revealed that transmembrane transport systems and DNA repair enzymes are inactivated after much shorter illumination periods than are intracellular enzymes. Although the pattern of photodynamic damage altered by varying the protocol of preincubation with hematoporphyrin-derivative and washing, it appeared that under all experimental conditions the plasma membrane was much more sensitive to photodynamic damage than were the intracellular enzymes. Lysosomal membrane disruption with subsequent detrimental release of lysosomal enzymes has been implicated previously in certain forms of porphyrin-induced photodynamic cell destruction. Cytochemical studies on enzyme localization virtually exclude such a mechanism in hematoporphyrin-derivative-induced cell inactivation in L929 fibroblasts.

Animals↗
PubMed1987

The role of hydroxyl radicals in the degradation of DNA by ozone.

The degradation of the nucleotides dAMP, dGMP, dCMP and dTMP and of calf thymus DNA by ozone was studied. In all cases both base and sugar moiety were degraded. Furthermore, strand breaks were induced in calf thymus DNA. Hydroxyl radicals were probably involved in the oxidation of the base in dAMP and of the deoxyribose ring, but not in the degradation of the other bases. This indicates that ozone-induced DNA damage proceeds both directly via ozone molecules and indirectly via hydroxyl radicals.

DNA Damage↗
PubMed1985

The influence of cupric ions on porphyrin-induced photodynamic membrane damage in human red blood cells.

Photooxidation of various susceptible substrates with hematoporphyrin derivative (photofrin) as sensitizer was strongly inhibited by simultaneous addition of cupric acetate to the reaction mixture. With sulfhydryl-containing compounds, however, an increased rate of photooxidation was observed under these experimental conditions. Preincubation of photofrin and cupric acetate at equimolar concentrations for 24 h at room temperature yielded a stable photofrin-Cu2+ complex. This complex did not act as photosensitizer with histidine, tryptophan, tyrosine, methionine or guanosine as substrates. With dithiothreitol, however, the photofrin-Cu2+ complex still acted as a photosensitizer, with an efficiency of about 30% as compared to free photofrin. Also in red blood cell membranes only sulfhydryl groups were photooxidized with the photofrin-Cu2+ complex as sensitizer. Illumination of intact erythrocytes in the presence of the photofrin-Cu2+ complex resulted in K+ leakage and, ultimately, photohemolysis. Pretreatment of the cells with N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited this photodynamically induced K+ loss. Considering recent studies on the reactivity of distinct membrane SH-groups with various sulfhydryl reagents this suggests that a sulfhydryl group, located in the 17 kDa membrane-bound fragment of band 3, is involved in photodynamic K+ leakage with the photofrin-Cu2+ complex as sensitizer.

Copper↗
PubMed1985

Site-specific and bulk-phase generation of hydroxyl radicals in the presence of cupric ions and thiol compounds.

Addition of a thiol compound to a solution containing Cu2+ and H2O2 resulted in the generation of hydroxyl radicals (OH.). These radicals were able to oxidize salicylic acid and tryptamine in a reaction that was strongly inhibited by the OH.-scavenger mannitol. Covalent coupling of the thiol compound to tryptamine did not significantly influence the degradation of the indole moiety subsequent to addition of H2O2 and Cu2+. The inhibiting effect of mannitol, however, was strongly reduced, indicating that the scavenger could not interfere with site-specific reactions of OH..

Copper↗
PubMed1985

Peroxide-induced membrane damage in human erythrocytes.

Erythrocytes exposed to H2O2 or t-butyl hydroperoxide (tBHP) exhibited lipid peroxidation and increased passive cation permeability. In the case of tBHP a virtually complete inhibition of both processes was caused by butylated hydroxytoluene (BHT), whereas pretreatment of the cells with CO increased both lipid peroxidation and K+ leakage. In the experiments with H2O2, on the other hand, both BHT and CO strongly inhibited lipid peroxidation, without affecting the increased passive cation permeability. These observations indicate different mechanisms of oxidative damage, induced by H2O2 and tBHP, respectively. The SH-reagent diamide strongly inhibited H2O2-induced K+ leakage, indicating the involvement of SH oxidation in this process. With tBHP, on the contrary, K+ leakage was not significantly influenced by diamide. Thiourea inhibited tBHP-induced K+ leakage, without affecting lipid peroxidation. Together with other experimental evidence this contradicts a rigorous interdependence of tBHP-induced lipid peroxidation and K+ leakage.

Butylated Hydroxytoluene↗
PubMed1985

Alternative-substrate inhibition of L-lactate transport via the monocarboxylate-specific carrier system in human erythrocytes.

The L-lactate/proton symport system of the red blood cell membrane was studied under conditions of alternative-substrate inhibition by glycolate. At constant pH of the medium glycolate caused competitive inhibition of L-lactate transport. In Lineweaver-Burk plots of 1/v against 1/[H], on the other hand, glycolate caused an uncompetitive inhibition. These observations indicate, that the monocarboxylate carrier exhibits ordered substrate binding, with the proton binding first.

Carrier Proteins↗
PubMed1980

Effects of semicarbazide on oxidative processes in human red blood cell membranes.

Semicarbazide can interfere with oxidative processes in the red blood cell membrane via different modes of action. Treatment of human red blood cell membranes with O3, results, among other effects, in cross-linking of membrane proteins and inhibition of glyceraldehyde-3-phosphate dehydrogenase activity. Semicarbazide inhibits these effects by acting as an O3 scavenger. The effect of semicarbazide as an O3 scavenger is complicated by the fact that ozonolysis of semicarbazide yields a product that causes inhibition of glyceraldehyde-3-phosphate dehydrogenase. Glyceraldehyde-3-phosphate dehydrogenase inhibition can also be provoked by incubation of membrane suspensions with O3-treated phospholipids. Semicarbazide prevented this effect by interaction with an inhibitory O3-phospholipid reaction product. Protoporphyrin-induced photodynamic cross-linking of membrane proteins is chemically distinct from O3-induced cross-linking. Photodynamic cross-linking is also inhibited by semicarbazide, in this case via reaction with a histidine photooxidation product.

Erythrocyte Membrane↗
PubMed1980

Kinetic analysis of simultaneously occurring proton-sorbose symport and passive sorbose transport in Saccharomyces fragilis.

Sorbose transport in Saccharomyces fragilis takes place both via an active sugar-H+ symport system and via facilitated diffusion. To establish whether the two modes of transport proceed via the same transporter or via two different carriers, the kinetic consequences of both models were investigated. The kinetic equations for initial transport were derived for three possible reaction sequences with respect to sugar and H+ binding to the symport carrier: random binding and obligatory ordered binding with either sugar or H+ binding first, yielding six sets of kinetic parameters. Analysis of experimental data of sorbose transport in S. fragilis showed the existence of separate carriers for active, sorbose-H+ symport and facilitated diffusion. Furthermore, it could be concluded that the symport carrier shows random binding of sugar and H+. In recent literature, a similar combination of active and passive sugar transport in Rhodotorula gracilis and Chlorella vulgaris was interpreted as two modes of action of the same carrier, viz., active symport via the protonated, and facilitated diffusion via the unprotonated carrier. Analysis of the experimental data according to the criteria presented in this paper showed, however, that this supposition is untenable and that two different carriers must also be involved in these micro-organisms.

Biological Transport↗